Background

Before the implementation of formal screening programs, congenital hearing impairment was historically difficult to detect. Many children were well over 2 years of age before significant hearing loss was identified, and therefore intervention was lacking during the critical time for language development. The incidence of congenital deafness is estimated at 1 to 3:1000 among term well babies and 2 to 4:1000 among infants with neonatal intensive care unit (NICU) admission.¹^–³ Identification of newborns with defective hearing and prompt intervention before 6 months of age has been shown to significantly improve both receptive and expressive language development. Universal Newborn Hearing Screening (UNHS) was established in the 1990s, and was endorsed by the American Academy of Pediatrics (AAP) in 1999. The AAP 2007 position paper recommends initial screening by 1 month of age. For those with a positive screen, comprehensive audiologic evaluation should occur by 3 months of age, with appropriate intervention by age 6 months for those with confirmed hearing loss (HL). Ongoing surveillance to include addressing parental concerns, middle ear examination, development, and behavior assessment of hearing for all children is recommended during routine well child visits beginning at age 2 months.⁴ Children at risk should be evaluated throughout childhood with repeat audiologic testing every 6 months until 3 years of age. Low-risk children should have routine surveillance and repeat hearing testing before kindergarten entry.³ An infant with delayed speech or concern for hearing impairment should be evaluated, even if a prior hearing screen was passed.⁴

Categories of Hearing Loss

There are three types of HL: sensorineural, conductive, and mixed. Sensorineural hearing loss (SNHL) includes the inner ear, cochlea, semicircular canals and internal auditory canals, the auditory nerve, the brainstem, and auditory neural pathway to the auditory cortex. Conductive hearing loss (CHL) involves impedance of sound through the outer and/or middle ear. Mixed HL is a combination of both.^1,² The magnitude of HL is classified by decibels (dB) of HL as mild, moderate, severe, or profound. Mild HL ranges from 20 to 40 dB, moderate from 40 to 60 dB, severe from 60 to 80 dB, and profound greater than 80 dB.

Newborn nursery screening programs have been instituted to identify bilateral and unilateral sensorineural HL and permanent conductive HL. Infants admitted to the NICU are screened for sensorineural HL, which may include a cochlear abnormality or auditory neuropathy/dyssynchrony (AN).⁴ AN is characterized by a normal response to sound (the cochlear hair cells are spared), but affected individuals are unable to process sounds (sound transmission in the eighth nerve is disordered); therefore the ability to understand speech and language is compromised.⁵

Screening Tests

Two screening tests for newborns are used: the automated auditory brainstem response (AABR) and the transient evoked otoacoustic emissions (OAE). They are noninvasive and record physiologic activity of normal auditory function. With OAE, an external ear probe (with a sensitive microphone) records cochlear outer hair cell responses to a series of soft clicks. Normal cochlear hairs respond to sound waves with echoes. The OAE measures response of these hair cells to the clicks, compares them to computerized standardized responses, and generates a pass or fail (i.e., refer). The status of the peripheral auditory system from the pinna to the cochlear outer hair cells is assessed. AABR measures action potentials in the auditory pathway from the peripheral hearing system, the eighth cranial nerve, and the brainstem to the level of the midbrain. Earphones emit a series of soft clicks. Three electrodes placed on the infant’s forehead, mastoid, and nape of the neck measure electroencephalographic wave activity generated by the cochlea, eighth nerve, and the lower brainstem auditory pathway. Neural responses are compared with computerized standardized responses, and a pass or fail is generated. Infants who fail the initial screen are given a repeat screen by 4 weeks of age. If the repeat screen is not passed, complete audiologic evaluation with a diagnostic auditory brainstem response (ABR) is the next diagnostic step.^3,⁴ If an infant fails complete audiologic testing, evaluation by a team of professionals, including a pediatric otolaryngologist, geneticist, early intervention educator, speech pathologist, and pediatric ophthalmologist is indicated, with appropriate intervention instituted by 6 months of age.

Limitations of Screening

Screening has several limitations. Only moderate to severe hearing loss is detected. Some who initially pass will later be shown to have some degree of HL. This may reflect progressive degeneration, as in asymptomatic congenital cytomegalovirus infection, or the limited sensitivity of the screening tools to detect mild HL. Neural conduction disorders or auditory neuropathy/dyssynchrony are not detected with OAE. Adverse environmental conditions can affect screening results; testing is facilitated in a quiet environment. An abnormal screen is repeated by 4 weeks of age, and systems need to be in place for follow-up of abnormal results, including communication with the pediatrician.

A one-step screening procedure uses a single technology, either OAE or AABR, and has a higher false-positive detection rate.⁴ A two-step program initially uses OAE, and retesting for those who do not pass is either a second attempt with OAE or an AABR. The two-step procedure is more expensive but has a lower false-positive rate; hence fewer infants are referred for unnecessary complete audiologic testing.⁴ If an infant is tested twice using OAE, or initially with OAE and then with AABR and passes the second test, the infant is considered to pass.⁴ If the initial AABR is not passed, the infant should not be rescreened using OAE, because there could be auditory neuropathy/dyssynchrony, which is undetected with OAE.

Infants who spend at least 5 days in the NICU are at risk for auditory neuropathy/dyssynchrony and should only be screened with AABR. All infants with a positive screen should be referred to audiology for diagnostic ABR. Both ears should be rescreened in those who refer in one ear. For an infant in the NICU with a risk factor such as hyperbilirubinemia requiring exchange transfusion or culture-positive sepsis, rescreening is recommended before discharge.

Differential Diagnosis

Nonsyndromic congential hearing loss	Craniofacial anomaly–associated hearing loss
Congenital syndrome–associated hearing loss	Congenital infection–associated hearing loss

Introduction

When I evaluate an infant with a positive newborn hearing screen, I perform a comprehensive evaluation that begins with a history and physical examination. I inquire if the parents have a written copy of the results and whether a second screen was performed. I realize congenital hearing loss is often due to a single gene mutation, but check for other causes such as a primary maternal cytomegalovirus (CMV) infection.^1,^4,⁶ Birth history is relevant if there was significant asphyxia requiring mechanical ventilation, severe hyperbilirubinemia, or admission to the neonatal intensive care unit (NICU).^1,⁶ The examination should focus on clues such as a craniofacial anomaly or dysmorphic features suggestive of a specific syndrome.^1,⁶ An infant with confirmed hearing loss is referred for comprehensive team evaluation for diagnosis of etiology and management, which may include hearing aid or eventual cochlear implant.^1,⁶ Definitive intervention by age 6 months of age will help maximize expressive and receptive language development.^1,^6,⁷

Clinical Entities: Medical Knowledge

Nonsyndromic Congenital Hearing Loss
Pϕ	Over 60 genetic loci have been identified that cause isolated hearing loss, and at least 70% are autosomal recessive. Some are mutations in the gap junction proteins β2 and β6. For example, a mutation of GJβ2, which encodes the connexin protein 26 in the cochlea, results in moderate to severe bilateral hearing loss.
TP	Normal-appearing child with a normal physical examination.
Dx	A confirmed positive hearing screen is followed up with a diagnostic avditory brainstem response (ABR).
Tx	The multidisciplinary team approach is described in detail above. The goal is to implement amplification and early intervention services by 6 months of age and to bring appropriate candidates to a tertiary facility for evaluation for cochlear implantation. See Nelson Essentials 10.

Craniofacial Anomaly–Associated Hearing Loss
Pϕ	There are a wide array of anomalies involving the auricle and external auditory canal associated with conductive hearing loss (CHL) and/or SNHL.
TP	There may be a malformed and/or misplaced pinna, atretic or absent external ear canal, and/or preauricular pits or appendages.
Dx	The evaluation at birth and beyond is diagnostic ABR, high-resolution imaging, and a skilled multidisciplinary team of professionals that includes audiology, otolaryngology, genetics, educators from early intervention, speech pathology, and ophthalmology, and perhaps plastic surgery. Specific imaging and genetic testing are determined on an individual basis.
Tx	Treatment is individualized based on the evaluation and may involve cochlear implant and/or reconstructive surgery. See Nelson Essentials 50.

Congenital Infection–Associated Hearing Loss
Pϕ	Several maternal infections can result in perinatal hearing loss. CMV: Both primary and reactivation infections occur during pregnancy. Primary infections are more likely to be transmitted to the neonate than reactivation infection (40% versus 1%), and there is greater likelihood of symptoms at birth that may be isolated progressive hearing progressive loss or a full-blown syndrome affecting the brain, eyes, liver, and skin. Toxoplasmosis: A primary infection in pregnancy with the protozoan Toxoplasma gondii can infect the fetus and either be asymptomatic or produce direct effects on the brain, eyes, liver, spleen, and skin. Syphilis: A maternal infection with the spirochete Treponema pallidum can cause congenital syphilis, and the newborn may range from asymptomatic to the protean manifestations outlined below.
TP	CMV: There may be asymptomatic infection with development of progressive SNHL or the full-blown syndrome with microcephaly, cranial periventricular calcifications, jaundice, hepatitis, petechiae and thrombocytopenia, seizures, abnormal muscle tone, and severe intellectual disability.
	Toxoplasmosis: At birth, 70% to 90% of infected infants are asymptomatic and normal appearing. The classic triad in symptomatic infants is chorioretinitis, hydrocephalus, and intracranial calcifications. Findings at birth may include fever, maculopapular rash, hepatosplenomegaly, seizures, jaundice, thrombocytopenia, microcephaly, and rarely generalized lymphadenopathy. Syphilis: Most with congenital infection are asymptomatic with a normal examination at birth. Fetal findings may include hydrops and stillbirth, with in utero death in up to 25% of cases. Early findings in the symptomatic newborn include rash on palms and soles, hepatosplenomegaly, jaundice, anemia, and “snuffles.” There may be periostitis and metaphyseal dystrophy noted on radiographs.
Dx	CMV: Urine CMV culture to be sent by 3 weeks of age to document congenital infection. Toxoplasmosis: Specific maternal and infant titers. Syphilis: Positive rapid plasma reagin (RPR) with a confirming specific treponemal test. A spinal tap is performed to exclude meningitis.
Tx	CMV: In the full clinical syndrome, ganciclovir has been used, in addition to supportive care to the extent needed, followed by early intervention for therapy and development tracking. The asymptomatic child with a confirmed case is monitored with hearing evaluations through age 6 years. Augmentative hearing-assist devices or cochlear implant may be indicated. Toxoplasmosis: There is no specific treatment, and supportive care and early intervention is provided as needed. Augmentative hearing-assist devices or cochlear implant may be indicated. Syphilis: Treatment is with parenteral penicillin. See Nelson Essentials 66.